Irritable bowel syndrome (IBS) is a highly prevalent functional disorder characterized by the presence of abdominal pain and discomfort and changes in bowel habits (diarrhea and/or constipation) in the absence of reliable biological markers. IBS represents a spectrum of conditions with dysregulation of visceral function and afferent sensation and an association to emotional factors and stress. This syndrome has been viewed as a disorder of the brain-gut axis but recently roles for enteric infection and intestinal inflammation have also been proposed. Ulcerative colitis (UC) shares the symptoms of IBS but is, in contrast to IBS, an obvious inflammatory mucosal disease of the colon. The insight that molecular crosstalk exists between immune, nervous and neuroendocrine systems has widened the perspective of the pathophysiology of inflammatory attacks on various organs, including the gut.
The nervous and immune systems have a common language based on small molecules-cytokines and neuro-transmitters/peptides. The enteric nervous system (ENS) is largely an independent system and its reflexes may work independent of brain influences. However, no nerves enter the gut epithelium and luminal stimuli must therefore be detected and translated to nerves by neuro-transmitters/peptides released by enterochromaffin (EC) cells. The EC cells store huge amounts of various neuropeptides and are in fact the largest endocrine organ in the body. Neuro-transmitters/peptides are co-stored with chromogranins, a family of granule-specific, water-soluble acidic proteins. This family comprises five members and among them chromogranin A (CGA) and chromogranin B (CGB) are the most frequent granins localized in secretory organelles of endocrine cells and neurons. Intracellular CGA and CGB might play central roles in the secretory process partly by acting as helper proteins in the packaging of peptides, hormones or neuropeptides.
In an attempt to elucidate the involvement of neurotransmitters/peptides in inflammatory bowel diseases (IBD) and functional bowel disorders like irritable bowel syndrome (IBS), clinical studies have been based on plasma measurements, immunohistochemistry or quantitation of the content of neuropeptides in mucosal biopsies. However, many of the results obtained have been conflicting. The lack of easily accessible methods to assess the involvement of neuropeptides in UC and IBD has hampered the clinical insight of the role neuropeptides may play in these conditions.